Transdermal Delivery of Vaccines and Therapeutic Proteins

The author reviews advances in technology that may soon allow transdermal delivery of two of the fastest growing drug classes on the pharmaceutical market. This article is part of a special Drug Delivery issue.

The benefits and drawbacks associated with traditional transdermal delivery are well known. Transdermal delivery is popular with patients; it is comfortable, convenient to use and non-intimidating. Unfortunately, passive transdermal patches are compatible with a relatively small number of drugs, all of which are small molecules and of low water solubility. Recent advances in the development of new transdermal delivery options seek to maintain the features of transdermal delivery that patients appreciate while increasing the number of compounds that can be delivered. Two of the fastest growing segments of the pharmaceutical market, vaccines and therapeutic proteins, have been targeted for transdermal delivery, and there may be therapeutic advantages associated with the transdermal delivery route for both.

Structurally and physiologically, the skin is an important part of the immune system, providing front-line defense against various environmental assaults. In particular, mammalian skin is a dynamic barrier that exists in a variety of densities, textures, and layers to negotiate external stimuli. The uppermost layer of the skin, the epidermis, is capped by the stratum corneum, a layer of flat, plate-like cells known as keratinocytes. These cells prevent dehydration and provide a physical and chemical barrier to the outside world, protecting underlying tissues from particulates, bacteria, and viruses. Overcoming the barrier properties of the stratum corneum has, historically, provided one of the most significant challenges to transdermal delivery of water-soluble compounds such as proteins, peptides, and vaccines. The epidermis, which lacks a microcirculatory structure, varies in thickness from approximately 20–100 µm (1–3).

The dermis, which lies beneath the epidermis, is sometimes characterized as having an upper section (the papillary dermis) and a lower section (the reticular dermis); altogether, the dermis is about 1.5–3 mm thick (1, 4). The dermis contains a network of collagen fibers as well as an upper and lower plexus of both blood vessels and lymph vessels. The dermis, in general, and the upper portion of the dermis, in particular, has the highest density of lymphatic capillaries in the body (3, 5–7). The dermis is the major site of fluid exchange between the blood, lymphatic capillaries and interstitial fluid (2).